The RPE cell plays a basic role in maintaining the structural and physiological integrity of the neural retina. Alterations in its structural and functional actions can result in loss of photoreceptors and vision. We have studied the RPE cell extensively as an important immunoregulatory cell within the posterior pole of the eye. Our research activities on RPE cells can be subdivided into three categories: normal cell function studies, cytokine interactions and infectious processes. Cytokines, such as interferon (IFN)-gamma and IL-2, are a group of specialized hormone-like proteins which exert profound influences on cellular development and on a variety of cellular functions. This project has concentrated on studying the ways in which cytokines interact with cells of the immune system and with cells in the ocular microenvironment. These studies indicate that cytokine-mediated activation of RPE cells may be a basic component of ocular immunity and an important aspect of RPE cell transplantation. During the past year, we have studied the interactions of cytokines and cyclooxygenase gene expression in HRPE cells. Increases in cyclooxygenase (COX-2) expression has been found in vivo associated with inflammation, rheumatoid arthritis, ischemia and various cancers. In this study we showed that COX-2 and its products, prostaglandins, were produced when human RPE cells were exposed to inflammatory cytokines. NF-kB signaling pathway played a role in this process. Furthermore, COX inhibitors, NSAIDS, significantly decreased COX-2 gene expression and prostaglandin production. These studies indicate that RPE cells may participate in normal and pathologic retinal conditions through the induction of COX-2 and suggest novel therapeutic approaches for immune-mediated retinal pathology.